POS1028 GUSELKUMAB MAINTAINS RESOLUTION OF DACTYLITIS AND ENTHESITIS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS THROUGH 2 YEARS FROM A PHASE 3 STUDY
Authors: P. Rahman, I. Mcinnes, A. Deodhar, G. Schett, P. J. Mease, M. Shawi, D. Cua, J. Sherlock, A. Kollmeier, X. L. Xu, Y. Jiang, S. Sheng, C. T. Ritchlin, D. Mcgonagle
Journal: Annals of the Rheumatic Diseases (2022)

Background Guselkumab (GUS), a selective inhibitor of IL-23, significantly improved the diverse manifestations of active psoriatic arthritis (PsA), including dactylitis and enthesitis, in DISCOVER (D)-1 &amp; 2 trials of patients (pts) with active PsA 1,2 , with maintenance of response rates through 1 year (yr). 3,4 Dactylitis and enthesitis, extra-articular manifestations of PsA, can be difficult to treat and cause significant disease burden. 5,6 Objectives To evaluate the ability of GUS to provide long-term resolution of dactylitis and enthesitis in pts with PsA through 2 yrs of D-2. Methods D-2 biologic naïve pts with active PsA were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS Q4W. Independent assessors evaluated dactylitis (total score: 0-60) and enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). These post hoc analyses assessed baseline (BL) frequency and severity of enthesitis in pts with dactylitis and dactylitis frequency in pts with enthesitis. Post BL, changes in dactylitis and LEI scores over time (least squares [LS] mean changes; analysis of covariance [ANCOVA]) and rates of resolution of dactylitis and enthesitis (Chi square correlation test) were determined in pts with these manifestations at BL (missing data imputed as no change/response). Results At BL, more D-2 pts had enthesitis (68%) than dactylitis (45%). At BL, 78% of pts with dactylitis vs 61% without (w/o) dactylitis had enthesitis and 51% of pts with enthesitis vs 32% w/o enthesitis had dactylitis. Among pts with enthesitis at BL, a higher percentage of pts with dactylitis (52%) had severe enthesitis (LEI score ≥3) vs pts w/o dactylitis (44%). Among those with the condition at BL, resolution rates of dactylitis (57%, Q4W; 64%, Q8W) and enthesitis (44%, Q4W; 54%, Q8W) at W24 increased through W52 (dactylitis: 74%, Q4W; 78%, Q8W; enthesitis: 57%, Q4W; 61%, Q8W) and were maintained at W100 (dactylitis: 72%, Q4W; 83%, Q8W; enthesitis: 62%, Q4W; 70%, Q8W). Consistent results were observed when evaluating mean changes in dactylitis and LEI scores and in pts who crossed over from PBO to GUS Q4W at W24 (Table 1). In pts with dactylitis and enthesitis at BL, GUS-treated pts showed significant correlations between resolution of enthesitis and dactylitis at W24 (p=0.004), W52 (p&lt;0.001) and W100 (p=0.039), with nearly 90% of pts with enthesitis resolution also achieving dactylitis resolution at W52 and W100 (Figure). Table 1. LS mean change from baseline over time in dactylitis and LEI scores in pts with manifestation at baseline GUS 100 mg Q4W GUS 100 mg Q8W PBO → GUS 100 mg Q4W Dactylitis score (0-60) Pts, N 121 111 99 W24 a -5.9 (-6.7, -5.0) -6.0 (-6.8, -5.1) -4.0 (-5.0, -3.1) W52 a -6.5 (-7.2, -5.8) -7.2 (-7.9, -6.5) -6.9 (-7.6, -6.2) W100 a -6.5 (-7.1, -5.8) -7.5 (-8.1, -6.8) -6.9 (-7.6, -6.2) LEI score (1-6) Pts, N 170 158 178 W24 a -1.5 (-1.8, -1.3) -1.6 (-1.8, -1.4) -1.0 (-1.3, -0.8) W52 a -1.8 (-2.0, -1.6) -1.9 (-2.1, -1.7) -2.0 (-2.2, -1.8) W100 a -1.9 (-2.1, -1.7) -2.1 (-2.3, -1.8) -2.1 (-2.3, -1.9) a Results are LS mean change (95% confidence interval [CI]); LS mean change determined by ANCOVA; missing data was imputed as no change for pts who discontinued treatment and using multiple imputation for remaining missing data GUS, guselkumab; LEI, Leeds Enthesitis Index; LS, least squares; PBO, placebo; pts, patients; Q4W, every 4 weeks; Q8W, every 8 weeks; W, week Conclusion Pts with PsA often present with concurrent enthesitis and dactylitis, both of which can be recalcitrant to treatment. GUS resolved enthesitis and dactylitis in substantial proportions of pts through W100. GUS-treated pts who achieved enthesitis resolution were more likely to achieve dactylitis resolution and vice versa. References [1]Deodhar A et al. Lancet. 2020;395:1115 [2]Mease PJ et al. Lancet . 2020;395:1126 [3]Ritchlin C et al. RMD Open . 2021;7(1):e001457 [4]McInnes IB et al. Arthritis Rheumatol . 2021;73:604 [5]Kaeley GS et al. Semin Arthritis Rheum . 2018;48:35 [6]McGonagle D et al. Nat Rev Rheumatol. 2019;15:113 Disclosure of Interests Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, Janssen, Novartis, and UCB, Grant/research support from: AstraZeneca, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Georg Schett Speakers bureau: Abbvie, Janssen, and Novartis, Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, May Shawi Shareholder of: Janssen Global Services, LLC, Employee of: Janssen Global Services, LLC, Daniel Cua Shareholder of: Janssen Research &amp; Development, LLC, Employee of: Janssen Research &amp; Development, LLC, Jonathan Sherlock Shareholder of: Janssen Research &amp; Development, LLC, Employee of: Janssen Research &amp; Development, LLC, Alexa Kollmeier Shareholder of: Janssen Research &amp; Development, LLC, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Janssen Research &amp; Development, LLC, Employee of: Janssen Research &amp; Development, LLC, Yusang Jiang Consultant of: Janssen, Employee of: Cytel Inc, Shihong Sheng Shareholder of: Janssen Research &amp; Development, LLC, Employee of: Janssen Research &amp; Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Dennis McGonagle Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB